Pathways

Mequitazine is a first-generation phenothiazine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Mequitazine is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Mequitazine inhibits the H1 histamine receptor on blood vessel endothelial cells. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin. Calcium bound calmodulin is required for the activation of the calmodulin-binding domain of nitric oxide synthase. The inhibition of nitric oxide synthesis prevents the activation of myosin light chain phosphatase. This causes an accumulation of myosin light chain-phosphate which causes the muscle to contract and the blood vessel to constrict, decreasing the swelling and fluid leakage from the blood vessels caused by allergens.

Mequitazine is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Mercaptopurine is an antimetabolite antineoplastic agent used for the treatment and immunosuppression of types of Leukemia, Crohn's disease, Hepatitis, Lymphoma and Ulcerative Colitis. It acts as a purine analogue that inferfere with the biosynthesis of nucleic acids. After oral administration, mercaptopurine is broken down into metabolites through many series of reactions and some of the metabolites interfere with the cell's function. Mercaptopurine has three main ways of causing immunosuppression. Firstly, the metabolite thiodeoxyguanosine-5'-triphosphate can become incorporated into DNA creating fraudulent information that cannot be used for replication or RNA transcription and translation. Second, thioguanosine 5'-triphosphate (not deoxy form) causes inhibition of ras-related c3 botulinum toxin substrate 1 which is a small GTPase protein on cell membranes that regulates many cellular events such as replication, cell to cell adhesion, epithelial differentiation, apoptosis, and more. Most importantly, it helps regulate the apoptosis of T and B lymphocytes so when ras-related c3 botulinum toxin substrate 1is inhibited, T and B cells undergo apoptosis since there is no regulation lowering the immune system. Lastly, 6-methylthiopurine 5'-monophosphate ribonucleotide/6-methylthioisonate, another mercaptopurine metabolite, inhibits amidophosphoribosyltransferase also known as glutamine-5-phosphoribosylpyrophosphate amidotransferase, which is a key enzyme in the purine de novo synthesis pathway. Amidophosphoribosyltransferase catalyzes the conversion of phosphoribosyl pyrophosphate into 5-phosphoribosylamine, the first commited step to the biosynthesis of purines. By inhibiting this step, adenine, adenosine, guanine and guanosine cannot be produced. Because T and B lymphocytes are reliant on the purine de novo pathway to obtain purines, inhibition causes them to die since they cannot proliferate quickly. Other cells can obtain purines form other sources, but T and B cells cannot.

Mercaptopurine is a purine antimetabolite prodrug that exerts cytotoxic effects via three mechanisms: via incorporation of thiodeoxyguanosine triphosphate into DNA and thioguanosine triphosphate into RNA, inhibition of de novo synthesis of purine nucleotides, and inhibition of Ras-related C3 botulinum toxin substrate 1, which induces apoptosis of activated T cells. Mercaptopurine travels through the bloodstream and is transported into cells via nucleoside transporters. Mercaptopurine is then converted to thioguanosince diphosphate through a series of metabolic reactions that produces the metabolic intermediates, thioinosine 5’-monophosphate, thioxanthine monophosphate, and thioguanosine monophosphate. Thioguanosine diphosphate is then converted via a thiodeoxyguanosine diphosphate intermediate to thiodeoxyguanosine triphosphate, which is incorporated into DNA. Thioguanosine diphosphate is also converted to thioguanosine triphosphate which is incorporated into RNA. The thioguanosine triphosphate metabolite also inhibits Ras-related C3 botulinum toxin substrate 1, a plasma membrane-associated small GTPase that regulates cellular processes, inducing apoptosis in activated T cells. Finally, de novo synthesis of purine nucleotides is inhibited by the methyl-thioinosine 5’-monophosphate metabolite, which inhibits amidophosphoribosyl-transferase, the enzyme that catalyzes one of the first steps in this pathway.

Mercaptopurine is an antimetabolic antineoplastic agent used in the treatment and maintenance therapy of acute lymphatic leukemia (ALL), acute promyelocytic leukemia, autoimmune hepatitis, Crohn's disease (CD), lymphoblastic lymphoma, and ulcerative colitis. This drug is a purine analogue, so it acts by interfering with the nucleic acid biosynthesis in cells. More specifically, this molecule is an analogue of the adenine and hypoxanthine bases. By being an analogue of those, mercaptopurine competes with them for the hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) enzyme and is itself converted to thioinosinic acid (TIMP). It is this metabolite that inhibits many reactions: among others, the conversion of inosinic acid to xanthylic acid and the conversion of IMP to adenylic acid (via the adenylosuccinate). There are 3 ways that this drug causes immunosuppression 1) One of the metabolites (thiodeoxyguanosine-5'-triphosphate) can be incorporated into DNA creating false information that cannot be used for replication or RNA transcription and translation, 2) Thioguanosine 5'-triphosphate (not deoxy form metabolite) causes inhibition of ras-related c3 botulinum toxin substrate 1, a small GTPase protein on the cell membranes. This protein regulates many events like replication, cell-to-cell adhesion, epithelial differentiation, apoptosis, and more. Most importantly, it helps the regulation of the apoptosis of T and B lymphocytes so when this substrate is inhibited, T and B cells undergo apoptosis since there is no regulation lowering the immune system. 3) the 6-methyl thiopurine 5'-monophosphate ribonucleotide/6-methylthioisonate, a mercaptopurine metabolite, inhibits amidophosphoribosyltransferase (glutamine-5-phosphoribosylpyrophosphate aminotransferase) which is a key enzyme in the purine de novo synthesis pathway. Amidophosphoribosyltransferase catalyzes the conversion of phosphoribosyl pyrophosphate into 5-phosphoribosylamine, the first committed step to the biosynthesis of purines. By inhibiting this step, adenine, adenosine, guanine, and guanosine cannot be produced. Because T and B lymphocytes are reliant on the purine de novo pathway to obtain purines, inhibition causes them to die since they cannot proliferate quickly. Other cells can obtain purines from other sources, but T and B cells cannot. An overdose of this drug would result in anorexia, nausea, vomiting, myelosuppression, liver dysfunction, and gastroenteritis. Mercaptopurine is administered as an oral suspension or tablet.

Mercaptopurine is a purine antimetabolite prodrug that exerts cytotoxic effects via three mechanisms: via incorporation of thiodeoxyguanosine triphosphate into DNA and thioguanosine triphosphate into RNA, inhibition of de novo synthesis of purine nucleotides, and inhibition of Ras-related C3 botulinum toxin substrate 1, which induces apoptosis of activated T cells. Mercaptopurine travels through the bloodstream and is transported into cells via nucleoside transporters. Mercaptopurine is then converted to thioguanosince diphosphate through a series of metabolic reactions that produces the metabolic intermediates, thioinosine 5’-monophosphate, thioxanthine monophosphate, and thioguanosine monophosphate. Thioguanosine diphosphate is then converted via a thiodeoxyguanosine diphosphate intermediate to thiodeoxyguanosine triphosphate, which is incorporated into DNA. Thioguanosine diphosphate is also converted to thioguanosine triphosphate which is incorporated into RNA. The thioguanosine triphosphate metabolite also inhibits Ras-related C3 botulinum toxin substrate 1, a plasma membrane-associated small GTPase that regulates cellular processes, inducing apoptosis in activated T cells. Finally, de novo synthesis of purine nucleotides is inhibited by the methyl-thioinosine 5’-monophosphate metabolite, which inhibits amidophosphoribosyl-transferase, the enzyme that catalyzes one of the first steps in this pathway.

Meropenem is a carbapenem antibiotic used to treat a wide variety of infections in the body. Meropenem is a broad-spectrum carbapenem antibiotic. It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. For use as single agent therapy for the treatment of the following infections when caused by susceptible isolates of the designated microorganisms: complicated skin and skin structure infections due to Staphylococcus aureus (b-lactamase and non-b-lactamase producing, methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (excluding vancomycin-resistant isolates), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and Peptostreptococcus species; complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species.Also for use in the treatment of bacterial meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (b-lactamase and non-b-lactamase-producing isolates), and Neisseria meningitidis. Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli and Pseudomonas aeruginosa; and PBPs 1, 2 and 4 of Staphylococcus aureus. Penicillin binding proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls.Inhibition of this protein leads to upregulation of autolytic enzymes and inhibition of cell wall synthesis. Meropenem is bactericidal and kills off the bacteria that it affects.